Interleukin-6 in Covid-19: A systematic review and meta-analysis.

Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated Covid-19, we undertook a systematic review and meta-analysis to assess the evidence in this field. We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in Covid-19; additional grey literature searches were undertaken. Study selection and data abstraction was undertaken independently by two authors. Meta-analysis was undertaken using random effects models to compute ratios of means with 95% confidence intervals (95%CIs). Eight published studies and two preprints (n = 1798) were eligible for inclusion. Meta-analysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated Covid-19 compared with patients with noncomplicated disease (six studies; n = 1302; 95%CI, 1.17-7.19; I2 = 100%). Consistent results were found in sensitivity analyses exclusively restricted to studies comparing patients requiring ICU admission vs no ICU admission (two studies; n = 540; ratio of means = 3.24; 95%CI, 2.54-4.14; P < .001; I2 = 87%). Nine of ten studies were assessed to have at least moderate risk of bias. In patients with Covid-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. Inhibition of IL-6 may be a novel target for therapeutics for the management of dysregulated host responses in patients with Covid-19 and high-quality studies of intervention in this field are urgently required.

A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by rapid human-to-human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS-CoV-2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID-19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID-19 epidemic include clear communication and education about hand hygiene, infection control measures, high-risk exposure, and the signs and symptoms of COVID-19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case-by-case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS-CoV-2 virology and epidemiology.

Skin cancer screening after solid organ transplantation: Survey of practices in Canada.

Guidelines recommend annual dermatology screening after solid organ transplantation to facilitate early detection of keratinocyte carcinoma (nonmelanoma skin cancer), the most common posttransplant malignancy. There are limited data on adherence levels and barriers to screening. We conducted a cross-sectional survey of 477 physicians and nurses providing posttransplant care in Canada. The questionnaire asked about skin cancer screening and education practices, including the perceived importance and barriers. Whereas care providers viewed skin cancer screening as important for adult patients (median rating of 10/10, interquartile range 8-10), only 53% ensured annual screening for white adult transplant recipients. Having a screening policy in place (adjusted odds ratio 6.78, 95% confidence interval 3.12-14.74) and a dermatologist present at the transplant center (adjusted odds ratio 2.19, 95% confidence interval 1.03-4.67) were independently associated with higher adherence. Long wait times, lack of specialized transplant dermatologists, long travel distances, and insufficient priority were cited as the most common barriers for access to dermatologic care. Skin cancer education was provided to patients by over three quarters of care providers. Given the self-reported lack of adherence to annual skin cancer screening, there is need to develop, evaluate, and implement interventions that improve screening rates and skin cancer outcomes.

Efficacy of Cidofovir in Treatment of BK Virus-Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.

BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.

An efficient strategy allowed English-speaking reviewers to identify foreign-language articles eligible for a systematic review.

OBJECTIVE: To assess English-speaking reviewers' accuracy in determining the eligibility of foreign-language articles for a systematic review. STUDY DESIGN AND SETTINGS: Systematic review of randomized controlled trials of therapy for fibromyalgia. Guided by 10 questions, English-speaking reviewers screened non-English-language articles for eligibility. Teams of two native-language speakers provided reference standard judgments of eligibility. RESULTS: Of 15,466 potentially eligible articles, we retrieved 763 in full text, of which 133 were published in 19 non-English languages; 53 trials published in 11 languages other than English proved eligible. Of the 53 eligible articles, English-language reviewers guided by the 10 questions mistakenly judged 6 as ineligible; of the 80 ineligible articles, 8 were incorrectly judged eligible by English-language reviewers (sensitivity=0.89; specificity=0.90). Use of a simple three-step rule (excluding languages with less than three articles, reviewing titles and abstracts for clear indications of eligibility, and noting the lack of a clearly reported statistical analysis unless the word "random" appears) led to accurate classification of 51 of 53 articles (sensitivity=0.96; specificity=0.70). CONCLUSION: Our findings show promise for limiting the need for non-English-language review teams in systematic reviews with large numbers of potentially eligible non-English-language articles.

Systematic review and network meta-analysis of interventions for fibromyalgia: a protocol.

BACKGROUND: Fibromyalgia is associated with substantial socioeconomic loss and, despite considerable research including numerous randomized controlled trials (RCTs) and systematic reviews, there exists uncertainty regarding what treatments are effective. No review has evaluated all interventional studies for fibromyalgia, which limits attempts to make inferences regarding the relative effectiveness of treatments. METHODS/DESIGN: We will conduct a network meta-analysis of all RCTs evaluating therapies for fibromyalgia to determine which therapies show evidence of effectiveness, and the relative effectiveness of these treatments. We will acquire eligible studies through a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, PsychINFO, PapersFirst, ProceedingsFirst, and the Cochrane Central Registry of Controlled Trials. Eligible studies will randomly allocate patients presenting with fibromyalgia or a related condition to an intervention or a control. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and complete full text reviews to determine eligibility, and subsequently perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-important outcomes when possible. To assess relative effects of treatments, we will construct a random effects model within the Bayesian framework using Markov chain Monte Carlo methods. DISCUSSION: Our review will be the first to evaluate all treatments for fibromyalgia, provide relative effectiveness of treatments, and prioritize patient-important outcomes with a focus on functional gains. Our review will facilitate evidence-based management of patients with fibromyalgia, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons.